Dilated cardiomyopathy (DCM) is a type of heart disease characterized by poor pumping function. DCM is the most common cause of heart failure and is also the leading reason for heart transplantation. Many causes of DCM are unknown and the disease may be mild to severe. Optimization of the drug regimen for DCM may take months to years, with some patient refractory to treatment, resulting in progressive heart failure, heart transplantation, or death. Since the drug regimen for DCM treatment frequently varies from patient to patient, the current lack of a model system in the dish prevents accurate validation of treatment plans and prediction of drug side- effects. Current validation of long-term treatment in the laboratory employs traditional electrophysiology, both a time-consuming and destructive method for interrogating heart cell electrical activity. In order to track the efficacy of applied drugs and detect potential long-term side-effects, what is needed is an engineered heart muscle (EHM) system that recapitulates the salient disease features of DCM and whose function can be both controlled and monitored acutely and chronically, precisely and non- destructively. To create this system, the candidate proposes (1) to create and characterize stem cell- derived heart cells that can be controlled and monitored with light, a technology called optogenetics; (2) to create and characterize optogenetic DCM-EHM made from these modified heart cells; and (3) to use optogenetic DCM-EHM to screen drugs that best mitigate the deleterious features of the disease. The candidate has a significant track record of research in optogenetics, stem cell biology, tissue engineering, and cardiovascular disease, and will expand his technical skills and career development activities by closely interacting with his faculty mentor, advisory committee, and collaborators in those areas. At the end of the K01 award, the candidate's goal is to successfully obtain R01 funding. Together, with full institutional support in a rich institutional environment, the mentor, advisory committee, and collaborators are fully committed to facilitating his successful transition to an independent investigator.